Celiac Disease: Exploring the Iceberg - PowerPoint PPT Presentation

About This Presentation
Title:

Celiac Disease: Exploring the Iceberg

Description:

Celiac Disease: Exploring the Iceberg Stefano Guandalini, M.D. Professor of Pediatrics Chief, Section of Gastroenterology, Hepatology and Nutrition – PowerPoint PPT presentation

Number of Views:399
Avg rating:3.0/5.0
Slides: 67
Provided by: downeastc
Category:

less

Transcript and Presenter's Notes

Title: Celiac Disease: Exploring the Iceberg


1
Celiac DiseaseExploring the Iceberg
  • Stefano Guandalini, M.D.
  • Professor of Pediatrics
  • Chief, Section of Gastroenterology, Hepatology
    and Nutrition
  • University of Chicago

2
Well talk about...
  • How we define celiac disease
  • Who gets it and how?
  • How common it is
  • What are its clinical manifestations
  • What conditions can accompany it
  • Complications
  • How it is diagnosed and treated

3
Definition
  • Celiac disease is a permanent condition affecting
  • primarily the intestine and caused by an abnormal
    reaction to gluten occurring in the immune
    (defense) system of the gut of individuals who
    possess
  • certain genes.
  • It leads to gastrointestinal and
    non-gastrointestinal symptoms, but it my as well
    be asymptomatic.

Indeed, celiac disease occurs more often in
people who have few or no symptoms!
4
Gluten
5
Where is gluten found?
6
Where is gluten found?
The Grass Family - (GRAMINEAE)
Subfamily Tribe
Festucoideae
Zizaneae Oryzeae Hordeae
Aveneae Festuceaea Chlorideae
wild rice rice wheat oat
finger millet teff
(ragi)
rye barley
7
And what exactly is it?
Gluten is made up by Gliadin and Glutenin
A (huge!) grain of wheat
Some well-identified pieces (called peptides)
of gliadin are resistant to digestion in the gut
and are toxic for celiac patients
8
Well talk about...
  • How we define celiac disease
  • Who gets it and how?
  • How common it is
  • What are its clinical manifestations
  • What conditions can accompany it
  • Complications
  • How it is diagnosed and treated

9
Who gets celiac disease?
Nothing....
10
Who gets Celiac Disease?
Celiac Disease
11
Breast feeding and celiac disease Odds ratios
(95 CI) of effect of breast feeding at the time
of gluten introduction on development of CD.
Akobeng AK et al., Arch Dis Child 2006
12
Timing of gluten introduction and risk of celiac
disease autoimmunity- A prospective study on
1560 children at risk
1307 children followed from birth 996 for cord
blood HLA-DR3 311 for FH of IDDM
253 children enrolled at age 2-3 for FH of IDDM
Interviews with telephone questionnaire At age 3,
6, 9, 12, 15 months
Same dietary information collected
retrospectively
Blood drawn for celiac serology (TG2) at 9, 15,
24 m and then annually
Blood drawn for celiac serology (TG2) at
enrollment and then annually
Norris JM et al., JAMA 2005
13
Timing of gluten introduction and risk of celiac
disease autoimmunity- A prospective study on
1560 children at risk
Norris JM et al., JAMA 2005
14
Does the amount of gluten matter?
15
Amount of gluten at weaning and celiac
diseaseThe Swedish experience
Ivarsson A et al., Eur J Epidemiol 2003
16
  • The rise in incidence was preceded by a twofold
    increase in the average daily consumption of
    gluten, and later the decline in incidence
    coincided with a consumption decrease by one
    third.

Hernell O et al., Celiac Disease Effect of
Weaning on Disease Risk, 2005
17
Take-home message celiac disease can be
prevented!
18
Does the timing of gluten introduction influence
the timing of appearance and/or the presenting
symptoms of celiac disease?
19
Breast feeding at time of gluten introduction
influences the presenting symptoms of celiac
disease
Plt0.01

Symptoms at diagnosis
Guandalini S., UCCDP n92 pts., in press
20
Changing pattern of celiac disease according to
age at presentation

Guandalini S., UCCDP n92 pts., in press
21
In summary, the role of environmental factors in
celiac disease
  • Breast feeding reduces the risk of celiac disease
    and/or at least delays its onset.
  • Introducing gluten at 4-6 months seems to be
    associated with the lowest risk of celiac
    disease.
  • Infants non breast-fed at the time of gluten
    introduction seem to be more likely to develop
    typical (GI) celiac disease.
  • To reduce risk of celiac disease, gluten should
    be introduced in small amounts.
  • Intestinal infections especially by Rotavirus
    increase the risk of developing celiac disease

22
Well talk about...
  • How we define celiac disease
  • Who gets it and how?
  • How common it is
  • What are its clinical manifestations
  • What conditions can accompany it
  • Complications
  • How it is diagnosed and treated

23
How common is celiac disease?
Geographic Area Prevalence on clinical diagnosis Prevalence on screening data
Brasil ? 1400
Denmark 110,000 1500
Finland 11,000 1130
Germany 12,300 1500
Italy 11,000 1184
Netherlands 14,500 1198
Norway 1675 1250
Sahara ? 170
Slovenia ? 1550
Sweden 1330 1190
United Kingdom 1300 1112
USA 110,000 1133

Currently accepted worldwide Prevalence (in
Caucasians) 1
Projected number of celiacs in North America
about 3,000,000 Actual number of known celiacs
about 50,000 For each known celiac there are 53
undiagnosed patients.
24
The Celiac Iceberg
Symptomatic Celiac Disease
Intestine is damaged
Silent Celiac Disease
Intestine appears normal
Latent Celiac Disease
Genetic susceptibility - DQ2, DQ8
Positive serology
25
Well talk about...
  • How we define celiac disease
  • Who gets it and how?
  • How common it is
  • What are its clinical manifestations
  • What conditions can accompany it
  • Complications
  • How it is diagnosed and treated

26
Clinical Manifestations
  • Gastrointestinal symptoms/signs (typical)
  • Non-gastrointestinal symptoms/signs (atypical)

Symptomatic Celiac disease
  • Celiac Disease may also be associated with other
    conditions,
  • and mostly with
  • Autoimmune disorders
  • Some syndromes

27
Gastrointestinal symptoms
  • Most common age of presentation 6-24 months
  • Chronic or recurrent diarrhea
  • Constipation
  • Anorexia
  • Failure to thrive or weight loss
  • Abdominal pain, bloating
  • Vomiting

28
Typical Celiac Disease
29
London, 1938
30
Children with Celiac Disease
31
Non Gastrointestinal symptoms
Most common age of presentation older child to
adult
  • Dermatitis Herpetiformis
  • Dental enamel hypoplasia
  • of permanent teeth
  • Osteopenia/Osteoporosis
  • Short Stature
  • Delayed Puberty
  • Iron-deficient anemia resistant to oral Fe
  • Liver disease
  • Arthritis
  • Neurological problems
  • Psychiatric Disorders
  • Women Sub-In-fertility and/or miscarriages
    and/or low birth babies

32
The list keeps growing
  • Idiopathic dilated cardiomyopathy
  • Pancreatitis (ESPGHAN 2007)
  • Cardiac valves involvement (ESPGHAN 2007)

33
Dermatitis Herpetiformis
  • Erythematous macules gt urticarial papules gt tense
    vesicles
  • Severe itching
  • Most have no GI symptoms
  • 75 Gluten dependent villous atrophy
  • Serology positive in only 30-40

34
Its not just DH!Other skin disorders possibly
associated with celiac disease
  • Urticaria
  • Hereditary angioneurotic edema
  • Cutaneous vasculitis
  • Erythema nodosum
  • Psoriasis
  • Vitiligo
  • Dermatomyositis
  • Alopecia aerata

Abenavoli L et al., World J Gastroenterol 2006
35
Dental Enamel Defects
Involve the permanent teeth and can be the only
presenting sign of Celiac Disease
36
Low bone density (Osteoporosis)
Normal Peak Bone Mass can be achieved at puberty
by celiac children on a GFD, but only if the diet
is strict!
37
Short Stature/Delayed Puberty
Can anyone guess how many children who are
short have celiac disease as cause of their
reduced height?
  • Short stature in children / teens
  • 10 of short children and teens are celiacs
  • Delayed onset of menstrual periods
  • ? Not uncommon in teen girls with untreated
    Celiac Disease

38
Anemia
  • Considered the most common non-GI manifestation
    in older teenagers and adults
  • 5-8 of adults with unexplained iron deficiency
    anemia have Celiac Disease
  • In children with newly diagnosed Celiac Disease
  • ? Anemia is very common
  • ? However, in children presenting with anemia
    only, celiac disease is not very frequent

39
Liver disease A study on 14,000 CD patients and
67,000 controls
  • Highly statistically (plt0.001) increased risk for
    the following conditions in celiac disease
    (occurring before and after diagnosis) is shown
    for
  • Acute and chronic hepatitis
  • Primary sclerosing cholangitis
  • Fatty liver
  • Liver failure
  • Liver cirrhosis or fibrosis
  • Primary biliary cirrhosis

Ludvigsson JF et al. Clin Gastroenterol Hepatol
2007
40
Arthritis and Neurological Problems
  • Arthritis in adults
  • Fairly common, including those on gluten-free
    diets
  • Juvenile chronic arthritis
  • Up to 3 have Celiac Disease
  • Neurological problems in teenagers and adults
  • Cerebellar ataxia (abnormal gait)
  • Peripheral neuropathies
  • Epilepsy with cranial calcifications

41
Asymptomatic
Silent Latent
  • Latent No symptomsNormal mucosaPositive
    Serology (elevated celiac antibodies in the
    blood)
  • Silent No symptoms Damaged mucosa
  • Positive serology(elevated celiac antibodies
    in the blood)

42
Well talk about...
  • How we define celiac disease
  • Who gets it and how?
  • How common it is
  • What are its clinical manifestations
  • What conditions can accompany it
  • Complications
  • How it is diagnosed and treated

43
Other conditions can be associated with celiac
disease
  • The prevalence of Celiac Disease is higher in
    patients who have the following
  • Relative of a celiac person
  • Certain genetic disorders or syndromes
  • Other autoimmune conditions

44
Associated Conditions
20
16
12
percentage
8
4
General Population
0
Relatives
IDDM
Thyroiditis
Down syndrome
45
Celiac Disease and Autoimmunity
The Prevalence Of Autoimmune Disorders Increases
As Diagnosis Is Delayed
p 0.000001
Age at diagnosis (years)
Ventura A et al., Gastroenterology 1999
46
Well talk about...
  • How we define celiac disease
  • Who gets it and how?
  • How common it is
  • What are its clinical manifestations
  • What conditions can accompany it
  • Complications
  • How it is diagnosed and treated

47
Major Complications of Celiac Disease
  • Refractory celiac disease and related disorders
  • Intestinal lymphoma

48
Effects of Diagnostic Delay and Adherence to GFD
on Mortality in Celiac Patients
Corrao et al., Lancet Aug 2001
49
  • The most important diagnostic test in CD is the
    suspicion of the disease.
  • NIH consensus 2004

50
The role of serology
51
  • Gliadin antibodies
  • Gliadin is the alcohol soluble fraction of gluten
  • Elicits a strong humoral response in CD
  • Anti-food protein antibodies, IgG and IgA
  • Known to be also often positive in
  • Milk protein allergy
  • Crohns disease
  • Post-gastroenteritis
  • GERD
  • Etc
  • Anti-Reticulin, Anti-Endomysium, Anti-tissue
    Transglutaminase Antibodies
  • IgA and IgG auto-antibodies

52
Anti-gliadin IgG Sensitivity 83-100
Average 93 Specificity 47-94 Average
71 Anti-gliadin IgA Sensitivity 51-100 Averag
e 79 Specificity 71-100 Average 89
53
Anti-Endomysium Antibodies (EMA) Sensitivity 88-1
00 Average 95 Specificity 98-100 Average
99 Anti-Tissue Transglutaminase Antibodies
(TTG) Sensitivity 78-100 Average
94 Specificity 96-100 Average 98
54
IgA Deficiency a common problem in celiac
patients
  • 5-7 of celiac patients are IgA-deficient, thus
    unable to produce any IgA autoantibodies (either
    EMA or TTG).
  • In this subset of patients, research shows that
    IgG-EMA and IgG-TTG can be detected and are as
    sensitive and as specific for the diagnosis of
    celiac disease.

Cataldo F et al., Gut 2000 Korponay-Szabo, Gut
2003 Dahlbom I, Clin Diagn Lab Immunol. 2005
55
CD Antibodies in other biological fluids?
Kappler M et al., BMJ 2006
56
Celiac
57
Histological Features
Normal 0
Infiltrative 1
Hyperplastic 2
Partial atrophy 3a
Subtotal atrophy 3b
Total atrophy 3c
58
Suggested Diagnostic Strategy I
Strong suspicion of CD? (Typical GI
presentation)
Do NOT initiate a gluten-free diet! Refer to
Pediatric GI for EGD with biopsies
59
Suggested Diagnostic Strategy II
  • Signs of possible extra-intestinal CD and/or
    associated conditions
  • Dental enamel hypoplasia
  • Recurrent aphtous stomatitis
  • Any autoimmune disorder (Diabetes, Hashimoto,
    SLE, etc.)
  • Short Stature/Delayed Puberty
  • Persistently Elevated AST/ALT
  • Epilepsy or Ataxia
  • Fe-resistant anemia
  • Weakness, fatigue, lethargy
  • Syndromes Down, Turner, Williams
  • Total IgA Deficiency
  • First-degree relative of a celiac or of a type 1
    diabetic
  • History of recurrent miscarriages

Patient in a group at risk?
Check tTG, total serum IgA
Positive
Negative
Refer to Pediatric GI for EGD with biopsies
No CD
60
Efficacy of the case-finding strategy
61
(No Transcript)
62
(No Transcript)
63
(No Transcript)
64
By applying simple and well-established criteria
for CD case finding on a sample of adults, we
achieved a 32- to 43-fold increase in the
diagnosis rate of this condition.
65
After diagnosis, use serology to monitor the
dietetic compliance of celiac patients
  • In adults, TTG and EMA are poor predictors of
    dietary transgressions
  • In children, TTG and AGA can both be used to
    monitor compliance AGA disappear before TTG
  • Periodic monitoring of serology is an integral
    component of proper follow-up in children with
    celiac disease

Vahedi Y et al., Am J Gastroenterol 2003 Cataldo
F et al., Acta Pediatr 1995 NASPGHAN guideline,
JPGN 2005
66
www.celiacdisease.net
Write a Comment
User Comments (0)
About PowerShow.com